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Artifacts arising when differential phase images are integrated is a common problem to several X-ray phase-based experimental techniques. The combination of noise and insufficient sampling of the high-frequency differential phase signal leads to the formation of streak artifacts in the projections, translating into poor image quality in the tomography slices. In this work, we apply a non-iterative integration algorithm proven to reduce streak artifacts in planar (2D) images to a differential phase tomography scan. We report on how the reduction of streak artifacts in the projections improves the quality of the tomography slices, especially in the directions different from the reconstruction plane. Importantly, the method is compatible with large tomography datasets in terms of computation time.

Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively. We have developed a system that can perform phase-based computed tomography (CT) scans in minutes, used it to image 101 specimens approximately half of which contained neoplastic lesions, and compared results against those of a commercial system. Histological analysis was carried out on all specimens and used as the gold standard. XPCI-CT showed higher sensitivity (83%, 95% CI 69–92%) than conventional specimen imaging (32%, 95% CI 20–49%) for detection of lesions at margin, and comparable specificity (83%, 95% CI 70–92% vs 86%, 95% CI 73–93%). Within the limits of this study, in particular that specimens obtained from surplus tissue typically contain small lesions which makes detection more difficult for both methods, we believe it likely that the observed increase in sensitivity will lead to a comparable reduction in the number of re-operations.

Recent trends in hard X-ray micro-computed tomography (microCT) aim at increasing both spatial and temporal resolutions. These challenges require intense photon beams. Filtered synchrotron radiation beams, also referred to as `pink beams', which are emitted by wigglers or bending magnets, meet this need, owing to their broad energy range. In this work, the new microCT station installed at the biomedical beamline ID17 of the European Synchrotron is described and an overview of the preliminary results obtained for different biomedical-imaging applications is given. This new instrument expands the capabilities of the beamline towards sub-micrometre voxel size scale and simultaneous multi-resolution imaging. The current setup allows the acquisition of tomographic datasets more than one order of magnitude faster than with a monochromatic beam configuration.

We present a dynamic implementation of the beam-tracking x-ray imaging method providing absorption, phase, and ultrasmall angle scattering signals with microscopic resolution and high frame rate. We demonstrate the method's ability to capture dynamic processes with 22-ms time resolution by investigating the melting of metals in laser additive manufacturing, which has so far been limited to single-modality synchrotron radiography. The simultaneous availability of three contrast channels enables earlier segmentation of droplets, tracking of powder dynamic, and estimation of unfused powder amounts, demonstrating that the method can provide additional information on melting processes.

Owing to their combination of low weight and high strength, carbon fiber reinforced composites are widely used in the aerospace industry, including for primary aircraft structures. Porosity introduced by the manufacturing process can compromise structural performance and integrity, with a maximum porosity content of 2% considered acceptable for many aerospace applications. The main nondestructive evaluation (NDE) techniques used in industry are ultrasonic imaging and X-ray computed tomography, however both techniques have limitations. Edge Illumination X-ray Phase Contrast Imaging (EI XPCi) is a novel technique that exploits the phase effects induced by damage and porosity on the X-ray beam to create improved contrast. EI XPCi is a differential (i.e., sensitive to the first derivative of the phase), multi-modal phase method that uses a set of coded aperture masks to acquire and retrieve the absorption, refraction, and ultra-small-angle scattering signals, the latter arising from sub-pixel sample features. For carbon fiber-reinforced woven composite specimens with varying levels of porosity, porosity quantification obtained through various signals produced by EI XPCi was compared to ultrasonic immersion absorption C-scans and matrix digestion. The standard deviation of the differential phase is introduced as a novel signal for the quantification of porosity in composite plates, with good correlation to ultrasonic attenuation.

Introduction Oesophageal cancer is the 7th commonest cause of cancer death worldwide. Radiological staging of local oesophageal cancer is inaccurate. CT currently relies on attenuation of x-rays to generate contrast. Soft tissues have very similar attenuation properties so minimal contrast is generated. X-ray phase contrast imaging (XPCI) uses refraction of x-rays as they pass through tissue instead of attenuation and provides much higher soft tissue contrast. This technology can be tuned to a resolution of approximately 10 µm. This may allow for easy assessment of extent of disease infiltration. We aimed to use XPCI to image oesophagectomy specimens to assess pathological tumour and nodal stage for oesophageal cancer Methods Following ethical approval, 10 oesophagectomy specimens were obtained from patients having surgery for oesophageal cancers. These included both squamous and adenocarcinomas. Specimens were fixed in formalin for 12 hours. Sutures were placed through tissue to enable co-registration between CT slices and histology sections. For some scans, tissue was then dehydrated with graded ethanol for between 4.5 hours and 72 hours before being imaged. A Rigaku (MicroMax 007) xray source was used at 40 kV and 20 mA; a detector with 50µm pixel size; and sample and detector masks made of graphite substrate with gold overlay. Phase contrast was generated using edge illumination technique. We reconstructed the images using MATLAB® software. Specimens were returned for clinical histopathological assessment allowing correlation between H&E slides and CT images. Results We have performed 25 scans on 10 oesophagectomy samples and correlated them with histology Scans of samples in formalin failed to show adequate contrast between oesophageal layers to enable tumour visualisation and staging. Infiltrating the tissue with ethanol led to much better image contrast. We could easily identify mucosa, submucosa and both layers of muscle in reconstructed CT images. We also identified tumour infiltration through tissue layers and destruction of normal oesophageal morphology (figure 1). This was confirmed histologically and could be recognised by radiologists blinded to pathological staging This is the first time that XPCI has been used to image human oesophageal tissue. We have demonstrated the feasibility of the technique and the possibility of obtaining high resolution images which mimic histology with the extra benefit of demonstrating three dimensional structure.

Purpose Image processing plays a fundamental role in the study of central nervous system, for example in the analysis of the vascular network in neurodegenerative diseases. Synchrotron X-ray Phase-contrast micro-Tomography (SXPCT) is a very attractive method to study weakly absorbing samples and features, such as the vascular network in the spinal cord (SC). However, the identification and segmentation of vascular structures in SXPCT images is seriously hampered by the presence of image noise and strong contrast inhomogeneities, due to the sensitivity of the technique to small electronic density variations. In order to help with these tasks, we implemented a user-friendly ImageJ plugin based on a 3D Gaussian steerable filter, tuned up for the enhancement of tubular structures in SXPCT images. Methods The developed 3D Gaussian steerable filter plugin for ImageJ is based on the steerability properties of Gaussian derivatives. We applied it to SXPCT images of ex-vivo mouse SCs acquired at different experimental conditions. Results The filter response shows a strong amplification of the source image contrast-to-background ratio (CBR), independently of structures orientation. We found that after the filter application, the CBR ratio increases by a factor ranging from ~6 to ~60. In addition, we also observed an increase of 35% of the contrast to noise ratio in the case of injured mouse SC. Conclusion The developed tool can generally facilitate the detection/segmentation of capillaries, veins and arteries that were not clearly observable in non-filtered SXPCT images. Its systematic application could allow obtaining quantitative information from pre-clinical and clinical images.

International audience; We report a qualitative study on central nervous system (CNS) damage that demonstrates the ability of X-ray phase contrast tomography (XPCT) to confirm data obtained with standard 2D methodology and permits the description of additional features that are not detected with 2D or other 3D techniques. In contrast to magnetic resonance or computed tomography, XPCT makes possible the high-resolution 3D imaging of soft tissues classically considered “invisible” to X-rays without the use of additional contrast agents, or without the need for intense processing of the tissue required by 2D techniques. Most importantly for studies of CNS diseases, XPCT enables a concomitant multi-scale 3D biomedical imaging of neuronal and vascular networks ranging from cells through to the CNS as a whole. In the last years, we have used XPCT to investigate neurodegenerative diseases, such as Alzheimer’s disease (AD) and multiple sclerosis (MS), to shed light on brain damage and extend the observations obtained with standard techniques. Here, we show the cutting-edge ability of XPCT to highlight in 3D, concomitantly, vascular occlusions and damages, close associations between plaques and damaged vessels, as well as dramatic changes induced at neuropathological level by treatment in AD mice. We corroborate data on the well-known blood-brain barrier dysfunction in the animal model of MS, experimental autoimmune encephalomyelitis, and further show its extent throughout the CNS axis and at the level of the single vessel/capillary.

Purpose In this work the performance of a compact multiresolution and multicontrast x-ray phase system based on edge illumination is investigated. It has been designed for small animal imaging and with a limited footprint for ease of deployment in laboratories. Methods The presented edge illumination system is based on a compact microfocus tungsten x-ray source combined with a flat panel detector. The source has a maximum output of 10 W when the minimum spot size of about 15 μm is used. The system has an overall length of 70 cm. A new double sample mask design, obtained by arranging both skipped and nonskipped configurations on the same structure, provides dual resolution capability. To test the system, we carried out computed tomography (CT) scans of a plastic phantom with different source settings using both single-image and multi-image acquisition schemes at different spatial resolutions. In addition, CT scans of an ex-vivo mouse specimen were acquired at the best identified working conditions to demonstrate the application of the presented system to small animal imaging. Results We found this system delivers good image quality, allowing for an efficient material separation and improving detail visibility in small animals thanks to the higher signal-to-noise ratio (SNR) of phase contrast with respect to conventional attenuation contrast. The system offers high versatility in terms of spatial resolution thanks to the double sample mask design integrated into a single scanner. The availability of both multi- and single-image acquisition schemes coupled with their dedicated retrieval algorithms, allows different working modes which can be selected based on user preference. Multi-image acquisition provides quantitative separation of the real and imaginary part of the refractive index, however, it requires a long scanning time. On the other hand, the single image approach delivers the best material separation and image quality at all the investigated source settings with a shorter scanning time but at the cost of quantitativeness. Finally, we also observed that the single image approach combined with a high-power x-ray source may result in a fast acquisition protocol compatible with in-vivo imaging.

Combining low weight and high strength, carbon fiber reinforced composites are widely used in the aerospace industry, including for primary aircraft structures. Barely visible impact damage can compromise the structural integrity and potentially lead to failures. Edge Illumination (EI) X-ray Phase Contrast imaging (XPCi) is a novel X-ray imaging technique that uses the phase effects induced by damage to create improved contrast. For a small cross-ply composite specimen with impact damage, damage detection was compared to ultrasonic immersion C-scans. Different defect types could be located and identified, verified from the conventional ultrasonic NDE measurement.

A crucial issue in the development of therapies to treat pathologies of the central nervous system is represented by the availability of non-invasive methods to study the threedimensional morphology of spinal cord, with a resolution able to characterize its complex vascular and neuronal organization. X-ray phase contrast micro-tomography enables a highquality, 3D visualization of both the vascular and neuronal network simultaneously without the need of contrast agents, destructive sample preparations or sectioning. Until now, high resolution investigations of the post-mortem spinal cord in murine models have mostly been performed in spinal cords removed from the spinal canal. We present here post-mortem phase contrast micro-tomography images reconstructed using advanced computational tools to obtain high-resolution and high-contrast 3D images of the fixed spinal cord without removing the bones and preserving the richness of micro-details available when measuring exposed spinal cords. We believe that it represents a significant step toward the in-vivo application. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

A significant number of patients receiving breast-conserving surgery (BCS) for invasive carcinoma and ductal carcinoma in situ (DCIS) may need reoperation following tumor-positive margins from final histopathology tests. All current intraoperative margin assessment modalities have specific limitations. As a first step towards the development of a compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast, we prove that the system’s dimensions can be reduced without affecting imaging performance. We analysed the variation in noise and contrast to noise ratio (CNR) with decreasing system length using the edge illumination x-ray phase contrast imaging setup. Two-(planar) and three-(computed tomography (CT)) dimensional imaging acquisitions of custom phantoms and a breast tissue specimen were made. Dedicated phase retrieval algorithms were used to separate refraction and absorption signals. A ‘single-shot’ retrieval method was also used, to retrieve thickness map images, due to its simple acquisition procedure and reduced acquisition times. Experimental results were compared to numerical simulations where appropriate. The relative contribution of dark noise signal in integrating detectors is significant for low photon count statistics acquisitions. Under constant exposure factors and magnification, a more compact system provides an increase in CNR. Superior CNR results were obtained for refraction and thickness map images when compared to absorption images. Results indicate that the ‘single-shot’ acquisition method is preferable for a compact CT intraoperative specimen scanner; it allows for shorter acquisition times and its combination of the absorption and refraction signals ultimately leads to a higher contrast. The first CT images of a breast specimen acquired with the compact system provided promising results when compared to those of the longer length system.

Potential exposure to toxic elements initially occurs during gestation and after birth via breast milk, which is the principal source of nutrients for infants during the first months of life. In this study, we evaluated whether maternal oral supplementation with a multi-strain probiotic product can protect infants from exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) via breast milk. In-vitro studies of the bacterial strains present in this probiotic product showed a high bacterial tolerance for As, Cd, Hg, and Pb, and good binding capacity for Cd, Hg, and Pb (72%, 81%, and 64%, respectively) within 1 h of contact. We evaluated concentrations (5 mg L−1 for Cd and Pb, and 2 mg L−1 for Hg) that largely exceeded the provisional tolerable weekly intake of these toxic elements via food or water applicable for human consumption. Changes in the levels of these elements in breast milk and newborn stools were evaluated in the control (orally supplemented with placebo) and experimental (orally supplemented with probiotic) groups at birth (t0), 15 days (t15), and 30 days (t30) after delivery. Elemental analysis of breast milk did not show significant differences between the control and experimental groups at different stages of lactation; however, stool samples obtained from newborns of mothers supplemented with the probiotic product showed that Cd levels were significantly reduced (by 26%) at t15 compared with the levels of the controls. Our data did not show an association between concentration of toxic elements in breast milk and that in newborn stools. Indeed, the concentration of Cd, Hg, and Pb in breast milk decreased during the lactation period, whereas the levels of these elements in newborn stools were stable over time. Although our in-vitro data indicate that the consortium of these probiotic strains can absorb toxic compounds, this study was limited by its small sample size and potential uncontrolled confounding effects, such as maternal diet and lifestyle. Therefore, we could not confirm whether prophylactic use of this probiotic product can reduce the absorption of toxic elements. The risk assessment in the studied population evidenced a margin of exposure (MOE) of 1, or between 1 and 10 for Pb, and lower than 50 for As. This poses a potential risk for breastfed infants, indicating that interventions aimed to avoid breastfeeding-related health risks remain a major challenge in public health. Keywords: Breast milk, Meconium, Probiotic, Biomonitoring, Toxic element, Risk assessment

Introduction Oesophageal cancer is the 5th commonest cause of cancer death in the UK. It accounts for 9,000 new cancer cases every year. Most oesophageal cancers are diagnosed at a late stage. Survival data shows that patients with early disease have a 37.5% 5 year survival compared to 8.4% and 4.9% for those with regional or distant disease.1 Histological diagnosis of oesophageal pathology is an expensive and time consuming process with high inter observer variability. X-ray imaging is inexpensive and has not previously been used for imaging of soft tissue due to poor contrast resolution. X-ray phase contrast imaging (XPCI) uses refraction of x-rays as they pass through a tissue rather than attenuation, which provides much higher soft tissue contrast2. It can also be tuned to have a depth resolution of between 5 μm and 10 mm. This may allow for easy assessment of extent of disease infiltration. Aims We aimed to use XPCI to image four types of oesophageal mucosa, normal squamous, non-dysplastic Barrett’s oesophagus, Barrett’s oesophagus with high-grade dysplasia and oesophageal adenocarcinoma. Methods Following ethical approval, twelve biopsies were obtained both from patients attending for endoscopy at UCLH as well as from the CRUK Cancer Centre Biobank. Biopsies were imaged at the Diamond Synchrotron in beamline i13 using an XPCI technique called free space propagation. We reconstructed the images using MATLAB® software. These CT images were compared to histology from matched biopsies taken at the time of endoscopy or the original histological diagnosis if biobank tissue was used. Results We successfully reconstructed CT images for all four tissue types achieving a resolution of ∼5 microns. We were able to identify normal layered squamous mucosa as well as changes within the structure of the biopsies including glands and goblet cells. The four tissue types appear to have quite different morphology. In addition, the three dimensional tissue structure could be clearly identified, with cancer being the most disorganised. This is the first time that XPCI has been used to image oesophageal biopsies. We have demonstrated the feasibility of the technique and the possibility of obtaining high resolution images which mimic histology with the extra benefit of demonstrating three dimensional structure. References “Oesophageal cancer incidence statistics | Cancer Research UK.” [Online]. Available: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/oesophageal-cancer/incidence#ref-5. [Accessed: 29-Jan-2019]. Olivo A, Gkoumas S, Endrizzi M, et al. Low-dose phase contrast mammography with conventional x-ray sources. Medical Physics 2013;40(9);90701. doi:10.1118/1.4817480

Edge illumination X-ray phase-contrast imaging makes use of two absorbing masks for precise beam shaping and analysis. As the system is being translated to clinical and industrial environments, a robust quantitative algorithm is required to keep the masks precisely aligned without the need of an expert operator. We present a model for how the illumination on the detector varies as one mask is moved relative to the rest of the system. This model is based on a superposition of known illumination patterns associated with misalignment in each degree of freedom. Through inversion of this model, quantitative estimates of the degree of misalignment can be obtained, and hence can show the position of optimal alignment. The precision of alignment achievable through model inversion was tested, showing at least an order of magnitude improvement when compared to the established mask alignment procedure. Precision of the alignment along the optical axis, and around the three rotational degrees of freedom were found to be [ ± 0 . 78 μ m , ± 0 . 17 mdeg, ± 5 . 08 mdeg, ± 2 . 39 mdeg] respectively, whereas the established procedure would be limited to [ ± 42 . 5 μ m , ± 6 . 69 mdeg, ± 348 mdeg, ± 195 mdeg]. Furthermore, the model allows the decomposition of residuals into random and systematic components, the latter enabling accurate evaluation of imperfections in the masks’ structure which have now become the main limiting factor in the final degree of alignment.

Ultrasonic imaging and radiography are widely used in the aerospace industry for non-destructive evaluation of damage in fibre-reinforced composites. Novel phase-based X-ray imaging methods use phase effects occurring in inhomogeneous specimens to extract additional information and achieve improved contrast. Edge Illumination employs a coded aperture system to extract refraction and scattering driven signals in addition to conventional absorption. Comparison with ultrasonic immersion C-scan imaging and with a commercial X-ray CT system for impact damage analysis in a small cross-ply carbon fibre-reinforced plate sample was performed to evaluate the potential of this new technique. The retrieved refraction and scattering signals provide complementary information, revealing previously unavailable insight on the damage extent and scale, not observed in the conventional X-ray absorption and ultrasonic imaging, allowing improved damage characterisation.

Iterative tomographic reconstruction has been established as a viable alternative for data analysis in phase-sensitive x-ray imaging based on the edge-illumination principle. However, previously published approaches did not account for drifts of optical elements during a scan, which can lead to artefacts. Up to now, the strategy to reduce these artefacts was to acquire additional intermediate flat field images, which were used to correct the sinograms. Here, we expand the theoretical model to take these effects into account and demonstrate a significant reduction of (ring)-artefacts in the final reconstructions, while allowing for a significant reduction of scan time and dose. We further improve the model by including the capability to reconstruct combined absorption and phase contrast slices, which we experimentally demonstrate to deliver improved contrast to noise ratios compared to previously employed single shot approaches.

The suppression of ring artifacts in x-ray computed tomography (CT) is a required step in practical applications; it can be addressed by introducing refined digital low pass filters within the reconstruction process. However, these filters may introduce additional ringing artifacts when simultaneously imaging pure phase objects and elements having a non-negligible absorption coefficient. Ringing originates at sharp interfaces, due to the truncation of spatial high frequencies, and severely affects qualitative and quantitative analysis of the reconstructed slices. In this work, we discuss the causes of ringing artifacts, and present a general compensation procedure to account for it. The proposed procedure has been tested with CT datasets of the mouse central nervous system acquired at different synchrotron radiation facilities. The results demonstrate that the proposed method compensates for ringing artifacts induced by low pass ring removal filters. The effectiveness of the ring suppression filters is not altered; the proposed method can thus be considered as a framework to improve the ring removal step, regardless of the specific filter adopted or the imaged sample.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

When considering the acquisition of experimental synchrotron radiation (SR) X-ray CT data, the reconstruction workflow cannot be limited to the essential computational steps of flat fielding and filtered back projection (FBP). More refined image processing is often required, usually to compensate artifacts and enhance the quality of the reconstructed images. In principle, it would be desirable to optimize the reconstruction workflow at the facility during the experiment (beamtime). However, several practical factors affect the image reconstruction part of the experiment and users are likely to conclude the beamtime with sub-optimal reconstructed images. Through an example of application, this article presents SYRMEP Tomo Project (STP), an open-source software tool conceived to let users design custom CT reconstruction workflows. STP has been designed for post-beamtime (off-line use) and for a new reconstruction of past archived data at user’s home institution where simple computing resources are available. Releases of the software can be downloaded at the Elettra Scientific Computing group GitHub repository https://github.com/ElettraSciComp/STP-Gui.